This Program Project deals with humoral and cellular studies of the IgA system in health and disease. The component projects represent an array of interrelated studies of the immune responses of the secretory and systemic IgA systems to environmental substances including food, bacterial and viral antigens in normal individuals and inpatients with abnormalities of the immune system. In normal adults daily production of IgA exceeds that of other immunoglobulin isotypes. Yet, from the functional point of view, the role of both, secretory and serum IgA in immune protection, and in regulation of immune responses is completely misunderstood. The proposed studies include: Project I: Common Mucosal System in Humans Project II: Immunopathogenesis of IgA Nephropathy Project III: Regulation of IgA Autoantibodies Project IV: B Cell Ontogeny and Fc alpha Receptors These projects are interrelated at both conceptional and technical levels because of the common interest of participating investigators in IgA physiology and immunopathology.